ABSTRACT ? Nonhuman Primate Core (NHP Core/ Core 1) The end of the HIV/AIDS epidemic will be achievable only when an effective vaccine regimen can achieve long-term protective immunity, similar to that of vaccines that have nearly eliminated other global pathogens. HIV acquisition risk begins in utero and continues through the period of breastfeeding, then starts again at the time of sexual debut and continues into adulthood. Prevention of HIV through adulthood will require an active vaccine that elicits persistent immunity. Yet, current HIV vaccine platforms have failed to induce highly- protective immunity in adults in preclinical and clinical studies. Excitingly, recent studies indicate that achieving durable, polyfunctional, and bnAb responses following HIV infection may be more easily achieved in infancy than in an adult immune system. Yet, gaps remain in our understanding of whether HIV vaccination in early life is advantageous for achievement of protective, long lasting HIV immunity. Because of its many similarities in development, physiology, immunology and pathogenesis, nonhuman primate (NHP) models of HIV infection are highly appropriate to explore these research questions. Thus, this HIVRAD Program will use the NHP model to test the hypothesis that HIV Env vaccine platforms administered in early life and boosted in pre- adolescence will achieve durable, polyfunctional, and mature immune responses that will be more efficacious at prevention of sexual transmission than immunization starting in preadolescence. In this renewal, the NHP Core will continue to support NHP studies in Project 1, ?Age-related impact on early life B cell lineage-designed SOSIP HIV Env vaccination? (P.I. Dr. S. Permar, Duke University) and Project 2, ?RNA vaccination in early life to induce potent and broad HIV Env-specific antibody responses? (P.I. Dr. K. De Paris, UNC-CH). Projects test the same hypothesis using 2 different vaccine platforms, SOSIP and mRNA-LNP, respectively. The Nonhuman Primate Core (NHP Core) is an integral component of the overall HIVRAD Program and provides direct support to the Projects by coordinating and implementing all the NHP experiments (including regulatory approvals, and all procedures related to immunizations and sample collections), and by developing/testing a repeated low-dose rectal SHIV challenge model in adolescent macaques to test vaccine efficacy. This Core has a longstanding track-record of collaboration with the 2 Project Leads/Overall P.I?s, and will communicate frequently with both Projects and other Cores to assure all the experimental needs are met with due diligence. The NHP Core uses the unique resources and infrastructure of the California National Primate Research Center (CNPRC), out of which it operates, and the expertise of the Core Lead and staff. The CNPRC is built on a service-oriented and interdisciplinary mission of advancing non-human primate models of human diseases and translational research. Resources at CNPRC include a large rhesus macaque breeding colony, experience with time-mated pregnancies, nursery-rearing of infant macaques, and all other procedures of monitoring and sample collections that are essential to the successful completion of the Projects.